Absolute configuration and biosynthesis of tiliacorine and tiliacorinine

Abstract

The incorporation of (±)-coclaurine, (±)-norcoclaurine, (±)-N-methylcoclaurine, and didehydro-N-methylcoclaurinium iodide into tiliacorinine and tiliacorine in Tiliacora racemosa Colebr. has been studied, and specific utilization of the (±)-N-methylcoclaurine demonstrated. The evidence shows that both ‘halves’ of these bases are derived from N-methylcoclaurine. Double-labelling experiments with (±)-N-methyl[1-³H,6-O-methyl-¹⁴C]coclaurine showed that the O-methyl function from one of the N-methylcoclaurine units is lost in the biotransformation into tiliacorine and tilacorinine. Experiments with (±)-N-[¹⁴C]methyl[1-³H]coclaurine demonstrated that the hydrogen atom at the asymmetric centre in the 1-benzyltetrahydroisoquinoline precursor is retained in the bioconversion into tiliacorine and tiliacorinine. Biosynthetic experiments with (R)- and (S)-N-methylcoclaurines established that tiliacorine has the S- and R-configuration at the asymmetric centres C-1 and C-1′, respectively, and tiliacorinine has the SS-configuration at both centres.